Saturday, July 31, 2021

FDA Approves Verkazia (cyclosporine ophthalmic emulsion) for the Treatment of Vernal Keratoconjunctivitis

Santen Inc., the U.S. subsidiary of Santen Pharmaceutical Co., Ltd. (hereinafter, Santen), a global company focused exclusively on eye care, today announced that the U.S. Food and Drug Administration (FDA) has approved Verkazia (cyclosporine ophthalmic emulsion) 0.1% eye drops for the treatment of vernal keratoconjunctivitis (VKC) in children and adults.


VKC is a rare and recurrent allergic eye condition, most common in children and adolescents, that causes severe inflammation of the surface of the eye. The symptoms of VKC – intense itching, painful eyes and light sensitivity – can prevent those affected from participating in everyday activities.1,2,3 Without adequate treatment, severe cases may result in corneal ulcers and even vision loss.4

“This is an important milestone in Santen’s aim to bring innovative solutions that protect vision for those affected by rare ophthalmic conditions, and is the first prescription product approval for Santen in the U.S. market,” said Tatsuya Kaihara, CEO of Santen Inc. and Head of Santen North America. “If left untreated, VKC is associated with symptoms such as eye pain and vision loss that can have detrimental impacts on those it affects, including on school attendance and academic performance. With this approval, doctors and patients in the U.S. now have an effective and sustainable treatment for this rare condition that may allow those affected to continue taking part in everyday activities.”

How Verkazia Works
Verkazia is a prescription-only, uniquely-formulated oil-in-water cationic emulsion that provides improved ocular bioavailability of cyclosporine, which has been shown to be effective in the management of VKC. It works by inhibiting T-cell activation and reducing the level of immune cells and mediators that cause the chronic, severe, potentially debilitating allergic inflammation of the ocular surface that is seen in those affected by VKC. Worldwide, Verkazia is available for the treatment of VKC in select countries across Asia, Europe, and North America.

Verkazia Clinical Data
The safety and efficacy of Verkazia for the treatment of VKC was evaluated in two randomized, multi-center, double-masked, vehicle-controlled, clinical trials (VEKTIS Study and NOVATIVE Study). In the VEKTIS study, patients with severe VKC were randomized to four times daily of Verkazia 1 mg/mL or two times daily (BID) of Verkazia 1 mg/mL and vehicle group for the first 4 months (Period 1). Similarly, in the NOVATIVE study, patients with moderate to severe VKC were randomized to QID of Verkazia 1 mg/mL or QID of cyclosporine ophthalmic emulsion 0.5 mg/mL and vehicle group for the first 1 month (Period 1). In both studies, patients randomized to the vehicle group were switched to Verkazia (QID or BID) from Month 4 to Month 12 in VEKTIS Study and to cyclosporine ophthalmic emulsion 0.5 mg/mL QID or 1 mg/mL from Month 1 to Month 4 in NOVATIVE Study (Period 2).

In the studies, Verkazia demonstrated improvements in inflammation of the cornea (keratitis score) and ocular itching. The most common adverse reactions reported in greater than 5 percent of patients were eye pain (12%) and eye pruritus (8%), which were usually transitory and occurred during instillation.

https://de.wikipedia.org/wiki/Ciclosporin
https://go.drugbank.com/drugs/DB00091

Friday, July 30, 2021

FDA Approves Kerendia (finerenone) for the Treatment of Patients with Chronic Kidney Disease Associated with Type 2 Diabetes

Bayer announced today the United States (U.S.) Food and Drug Administration (FDA) has approved Kerendia (finerenone), a first-in-class nonsteroidal mineralocorticoid receptor antagonist (MRA) indicated to reduce the risk of sustained eGFR decline, kidney failure, cardiovascular death, non-fatal myocardial infarction (MI) and hospitalization for heart failure in adult patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D).1 The approval is based on the results of the pivotal Phase III FIDELIO-DKD trial data that demonstrated positive kidney and cardiovascular outcomes in patients with CKD associated with T2D, published in the New England Journal of Medicine in October 2020, and follows priority review designation granted by the FDA.1,6







The patient population included in the trial that supported the approval of Kerendia were at risk of chronic kidney disease progression despite receiving standard of care treatment to control blood pressure and blood glucose,”1,6 said George Bakris, M.D., University of Chicago and lead FIDELIO-DKD study investigator. “In people with chronic kidney disease associated with type 2 diabetes, physicians now have a new treatment to provide kidney protection.”1,3,6

The Kerendia label contains a Warning and Precaution that Kerendia can cause hyperkalemia.1 For more information, see "Important Safety Information" below.

Despite guideline-directed therapies, many people with CKD associated with T2D are at risk for CKD progression and cardiovascular events.2,3,4,5 Type 2 diabetes is the leading cause of end stage kidney disease, when patients may need dialysis or a kidney transplant to stay alive.7,8,9 Blacks or African Americans and Hispanic Americans have higher rates of kidney failure than their non-Hispanic white counterparts.10

Kerendia works by blocking overactivation of the mineralocorticoid receptor (MR). Mineralocorticoid receptor overactivation is thought to contribute to fibrosis and inflammation.1 Fibrosis and inflammation can contribute to permanent structural kidney damage.4,11

“Kerendia is the first and only nonsteroidal mineralocorticoid receptor antagonist proven to significantly slow chronic kidney disease progression and reduce cardiovascular risk in people with chronic kidney disease associated with type 2 diabetes,”1,6 said Amit Sharma, M..D, Vice President of Cardiovascular and Renal, Bayer U.S. Medical Affairs. “We are excited to bring this new kidney-focused treatment to people living with this condition.”1

“Chronic kidney disease associated with type 2 diabetes can have such a debilitating impact on patients’ lives.10 Unfortunately, this disease is far reaching, as up to 40 percent of all patients with type 2 diabetes develop chronic kidney disease,”12 said Kevin Longino, CEO, National Kidney Foundation, and a kidney transplant patient. “It is important for physicians and patients to have new treatment options that can slow chronic kidney disease progression.”

Kerendia is expected to be available in the U.S. beginning the end of July 2021. Finerenone has also been submitted for marketing authorization in the European Union.

About Kerendia

INDICATION:

  • Kerendia is indicated to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, non-fatal myocardial infarction, and hospitalization for heart failure in adult patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D).1

https://en.wikipedia.org/wiki/Finerenone

Thursday, July 29, 2021

FDA Approves Bylvay (odevixibat) for the Treatment of Pruritus in Patients with Progressive Familial Intrahepatic Cholestasis (PFIC)

Albireo Pharma, Inc. (Nasdaq: ALBO), a rare liver disease company developing novel bile acid modulators,  announced that, U.S. Food & Drug Administration (FDA) approval of Bylvay (odevixibat), the first drug approved for the treatment of pruritus in all subtypes of progressive familial intrahepatic cholestasis (PFIC). Bylvay is a potent, non-systemic ileal bile acid transport inhibitor (IBATi), which does not require refrigeration and is easily administered as a once-daily capsule or opened and sprinkled onto soft foods. Albireo is launching Bylvay immediately to accelerate availability for the patients and families impacted by PFIC.



“Treating children with PFIC can be difficult and frustrating given the current treatment options. Bylvay gives us a non-surgical option and will change how we treat PFIC,” said Richard Thompson, Professor of Molecular Hepatology at King’s College London and principal investigator of PEDFIC 1 and PEDFIC 2. “With this approval, my colleagues and I now have the opportunity to revisit how PFIC patients are being managed and we are hopeful for better outcomes for these children.”

PFIC is a rare and devastating disorder affecting young children that causes progressive, life-threatening liver disease. In many cases, PFIC leads to cirrhosis and liver failure within the first 10 years of life. The most prominent and problematic ongoing manifestation of PFIC is pruritus, or intense itching, which often results in a severely diminished quality of life. Until now, there have been no approved drugs for PFIC. Only surgical options that include biliary diversion surgery (BDS) and liver transplantation have been available, and without them, most PFIC patients do not survive past the age of 30. There are an estimated 100,000 patients with cholestatic liver disease without an approved drug treatment. Of those patients, there are approximately 15,000 with PFIC (excluding China and India).

“Until now invasive surgery was the only approved treatment option. With the approval of Bylvay, parents may find hope in having a less invasive treatment option available,” said Emily Ventura, leader of PFIC Advocacy and Resource Network (www.pfic.org) and mother to a PFIC patient. “As a community, we experience extreme challenges and diminished quality of life for children and families with PFIC. Managing the symptoms can be extremely difficult -- the burden is unimaginable with our kids suffering physically, emotionally and developmentally.”

The approval of Bylvay was supported by data from PEDFIC 1 and PEDFIC 2, the largest, global, Phase 3 trials ever conducted in PFIC. In PEDFIC 1, a randomized, double-blind, placebo-controlled study, Bylvay met both its pruritus (p=0.004) and serum bile acid (p=0.003) primary endpoints and was well tolerated with very low incidence of diarrhea/frequent bowel movements (9.5% of treated patients vs. 5.0% of placebo patients). PEDFIC 2, a long-term, open-label Phase 3 extension study, reaffirmed Bylvay delivered sustained reductions in serum bile acids as well as improvements in pruritus assessments, growth and other markers of liver function in patients treated up to 48 weeks. Across both studies, Bylvay was well tolerated with diarrhea/frequent stools being the most common treatment-related gastrointestinal adverse events. There were no serious treatment-related adverse events.

“Bylvay is the first ever approval by the FDA of a drug developed for a pediatric cholestatic liver disease and provides a non-surgical treatment for patients living with the burden of PFIC,” said Ron Cooper, President and CEO of Albireo. “We’re humbled by the children, families and investigators whose commitment to our clinical trials will bring hope and treatment benefit for so many future patients.”

Ready for Bylvay Launch
Bylvay is expected to be packaged and shipped within the coming days. With the immediate Bylvay launch, Albireo is ready with a focus on access and reimbursement, sales promotion, and patient support. To support payor decision-making, Albireo is submitting a compelling value package with the PEDFIC, gold standard, Phase 3 data, which includes long-term data with patients on drug for over two years; natural history information; and a caregiver study to reflect the burden of PFIC.

Sales promotion will begin immediately. The Albireo and Travere Therapeutics sales representatives will rapidly cover the 60 key centers to inform them of the availability of Bylvay for the treatment of pruritus in PFIC and patient access services.

https://en.wikipedia.org/wiki/Odevixibat

Wednesday, July 28, 2021

FDA Approves Rezurock (belumosudil) for the Treatment of Patients with Chronic Graft-Versus-Host Disease (cGVHD)

Kadmon Holdings, Inc.  announced the  U.S. Food and Drug Administration (FDA)  approval of Rezurock™ (belumosudil) 200 mg once daily (QD) for the treatment of adult and pediatric patients 12 years and older with chronic graft-versus-host disease (cGVHD) after failure of at least two prior lines of systemic therapy. The FDA granted Breakthrough Therapy designation and Priority Review for Rezurock and reviewed the New Drug Application (NDA) under the Real-Time Oncology Review (RTOR) pilot program. The FDA approved this NDA six weeks ahead of the Prescription Drug User Fee Act (PDUFA) goal date of August 30, 2021. Rezurock is the first and only FDA-approved small molecule inhibitor of ROCK2, a signaling pathway that modulates inflammatory responses and fibrotic processes.



"Rezurock represents a new treatment paradigm for thousands of cGVHD patients, including those with difficult-to-treat manifestations like fibrosis," said Corey Cutler, MD, MPH, FRCPC, Associate Professor of Medicine at Harvard Medical School and Medical Director, Adult Stem Cell Transplantation Program at the Dana-Farber Cancer Institute. "Rezurock has shown robust and durable responses across the spectrum of cGVHD and is safe and well tolerated, allowing patients to stay on therapy and achieve meaningful benefit from treatment."

The FDA approval of Rezurock is based on safety and efficacy results from ROCKstar (KD025-213), a randomized, open-label, multicenter pivotal trial of Rezurock in patients with cGVHD who had received two to five prior lines of systemic therapy. There were 65 patients treated with Rezurock 200 mg taken orally QD. The median time from cGVHD diagnosis was 25.3 months and 48% of patients had four or more organs involved. Patients had cycled through a median of 3 prior lines of systemic therapy and 78% were refractory to their last therapy. Rezurock 200 mg QD achieved an Overall Response Rate (ORR) of 75% through Cycle 7 Day 1 of treatment (95% Confidence Interval (CI): 63, 85), with 6% achieving a complete response and 69% achieving a partial response. The median time to first response was 1.8 months. Sixty-two percent (62%) of responders did not require new systemic therapy for at least 12 months following response. The median duration of response, calculated from first response to progression, death, or new systemic therapies for chronic GVHD, was 1.9 months. ORR results were supported by clinically meaningful improvement from baseline in the Lee Symptom Scale (LSS) score, a chronic GVHD symptom measurement, in 52% of patients through Cycle 7 Day 1 of treatment.

"Patients receiving Rezurock reported significant improvements in cGVHD symptoms, showing that not only did treatment result in organ responses, but it also made people feel better. This is so important for a chronic disease with a high symptom burden," said Stephanie Lee, MD, MPH, Professor at the Fred Hutchinson Cancer Research Center and the University of Washington School of Medicine, and Research Director of the Long-Term Follow-Up Program at Fred Hutchinson.

Rezurock has been well tolerated and adverse events have been consistent with those expected in patients with advanced cGVHD receiving corticosteroids and/or other immunosuppressants.

"We are proud to introduce Rezurock as a new treatment that uniquely addresses the underlying inflammatory and fibrotic pathophysiology of chronic GVHD," said Harlan W. Waksal, MD, President and CEO of Kadmon. "Thank you to the patients, their families and caregivers, who are the center of our focus in achieving this significant milestone. We have built a hematology/oncology-experienced commercial team and we look forward to rapid adoption of Rezurock for patients in need."

Rezurock is expected to be available in the United States by late August 2021.

Kadmon is committed to helping patients with treatment access and support. Kadmon ASSIST™ is a program designed to help and support Rezurock patients and their caregivers throughout their treatment journey. This program provides reimbursement assistance and savings programs for eligible patients. For more information, please call 1-844-KADMON1 (1-844-523-6661), Monday-Friday, 8:00 a.m.to 8:00 p.m. ET.

The NDA for Rezurock is part of Project Orbis, an initiative of the FDA Oncology Center of Excellence that provides a framework for concurrent submission and review of oncology drugs among participating international health authorities.

https://en.wikipedia.org/wiki/Belumosudil

Tuesday, July 27, 2021

FDA Approves Fexinidazole as the First All-Oral Treatment for Sleeping Sickness

In continuation of my update on fexinidazole


The US Food and Drug Administration (FDA) has approved fexinidazole as the first all-oral treatment for both stages of the Trypanosoma brucei gambiense form of sleeping sickness (Human African trypanosomiasis) in patients 6 years of age and older and weighing at least 20 kg.



Fexinidazole was developed as part of an innovative partnership between the non-profit research and development organization Drugs for Neglected Diseases initiative (DNDi), which conducted the pivotal clinical trials for this treatment, in partnership with the National Sleeping Sickness Programs of the Democratic Republic of Congo (DRC) and Central African Republic (CAR), and Sanofi.

Sleeping sickness is a parasitic disease transmitted by the bite of an infected tse-tse fly. It affects mostly populations living in remote rural areas of sub-Saharan Africa, where about 65 million people are at risk of infection. Left untreated, sleeping sickness is almost always fatal. Through Sanofi’s collaboration the number of sleeping sickness cases reported to the WHO has been reduced by ~97% between 2001 and 2020. DNDi, Sanofi and partners are deeply committed to ensuring access to fexinidazole in all sleeping sickness-endemic countries.

Current treatment options for the disease are effective, but burdensome for patients and health workers due to the need for infusion or injection, requiring hospitalization, especially challenging for people living in remote areas.

“Having a simple, all-oral treatment for sleeping sickness is a dream come true for frontline clinicians,” said Dr Bernard P├ęcoul, DNDi Executive Director. “We are proud of this latest milestone in our long-term partnership with Sanofi, developed in close collaboration with researchers in countries hard-hit by sleeping sickness.”

Fexinidazole is indicated as a 10-day once-a-day treatment for Trypanosoma brucei gambiense sleeping sickness, the most common form of the disease found in West and Central Africa. Fexinidazole is the first all-oral treatment that works both for the first stage of the disease, as well as the second stage of the disease in which the parasites have crossed the blood-brain barrier, causing patients to suffer from neuropsychiatric symptoms.

“This FDA approval is a key milestone in Sanofi’s long-term commitment to fight sleeping sickness, started 20 years ago alongside the WHO through an ambitious partnership to combat Neglected Tropical Diseases” said Luc Kuykens, Senior Vice President, Sanofi Global Health unit. “Following the positive scientific opinion granted by the European Medicines Agency end 2018, the FDA approval is an important step to revitalize efforts to support the sustainable elimination of the disease”.

As a result of FDA approval, a Tropical Disease Priority Review Voucher (PRV) has been awarded to DNDi. The FDA Tropical Disease PRV Program was established in 2007 to incentivize development of new treatments for neglected tropical diseases, including sleeping sickness. Any benefits from the PRV will be shared between Sanofi and DNDi, which will enable continued investments in innovating for and ensuring access to new health tools for sleeping sickness and other neglected diseases. Sanofi commits to continue to provide the drug free-of-charge to the World Health Organization for distribution to affected countries, as part of a long-term collaboration with WHO.

About Sleeping sickness
Sleeping sickness, or human African trypanosomiasis (HAT), is usually fatal without treatment. Transmitted by the bite of an infected tse-tse fly, following a period with nonspecific symptoms, it evolves to cause neuropsychiatric symptoms, including abnormal behaviour, and a debilitating disruption of sleep patterns that have given this neglected disease its name. About 65 million people in sub-Saharan Africa are at moderate to very high risk of infection.

About DNDi
The Drugs for Neglected Diseases initiative (DNDi) is a collaborative, patient needs-driven, not-for-profit research and development (R&D) organization that develops safe, effective, and affordable treatments for sleeping sickness, leishmaniasis, Chagas disease, filarial infections, mycetoma, paediatric HIV, hepatitis C, and covid-19. Since its inception in 2003, DNDi has delivered eight new treatments, including nifurtimox-eflornithine combination therapy (NECT) for late-stage sleeping sickness, and fexinidazole, the first all-oral drug for sleeping sickness.

https://en.wikipedia.org/wiki/Fexinidazole

Monday, July 26, 2021

FDA Approves Rezurock (belumosudil) for the Treatment of Patients with Chronic Graft-Versus-Host Disease (cGVHD)


Kadmon Holdings, Inc. (Nasdaq:KDMN) today announced that the U.S. Food and Drug Administration (FDA) has approved Rezurock™ (belumosudil) 200 mg once daily (QD) for the treatment of adult and pediatric patients 12 years and older with chronic graft-versus-host disease (cGVHD) after failure of at least two prior lines of systemic therapy. The FDA granted Breakthrough Therapy designation and Priority Review for Rezurock and reviewed the New Drug Application (NDA) under the Real-Time Oncology Review (RTOR) pilot program. The FDA approved this NDA six weeks ahead of the Prescription Drug User Fee Act (PDUFA) goal date of August 30, 2021. Rezurock is the first and only FDA-approved small molecule inhibitor of ROCK2, a signaling pathway that modulates inflammatory responses and fibrotic processes.

"Rezurock represents a new treatment paradigm for thousands of cGVHD patients, including those with difficult-to-treat manifestations like fibrosis," said Corey Cutler, MD, MPH, FRCPC, Associate Professor of Medicine at Harvard Medical School and Medical Director, Adult Stem Cell Transplantation Program at the Dana-Farber Cancer Institute. "Rezurock has shown robust and durable responses across the spectrum of cGVHD and is safe and well tolerated, allowing patients to stay on therapy and achieve meaningful benefit from treatment."

The FDA approval of Rezurock is based on safety and efficacy results from ROCKstar (KD025-213), a randomized, open-label, multicenter pivotal trial of Rezurock in patients with cGVHD who had received two to five prior lines of systemic therapy. There were 65 patients treated with Rezurock 200 mg taken orally QD. The median time from cGVHD diagnosis was 25.3 months and 48% of patients had four or more organs involved. Patients had cycled through a median of 3 prior lines of systemic therapy and 78% were refractory to their last therapy. Rezurock 200 mg QD achieved an Overall Response Rate (ORR) of 75% through Cycle 7 Day 1 of treatment (95% Confidence Interval (CI): 63, 85), with 6% achieving a complete response and 69% achieving a partial response. The median time to first response was 1.8 months. Sixty-two percent (62%) of responders did not require new systemic therapy for at least 12 months following response. The median duration of response, calculated from first response to progression, death, or new systemic therapies for chronic GVHD, was 1.9 months. ORR results were supported by clinically meaningful improvement from baseline in the Lee Symptom Scale (LSS) score, a chronic GVHD symptom measurement, in 52% of patients through Cycle 7 Day 1 of treatment.

"Patients receiving Rezurock reported significant improvements in cGVHD symptoms, showing that not only did treatment result in organ responses, but it also made people feel better. This is so important for a chronic disease with a high symptom burden," said Stephanie Lee, MD, MPH, Professor at the Fred Hutchinson Cancer Research Center and the University of Washington School of Medicine, and Research Director of the Long-Term Follow-Up Program at Fred Hutchinson.

Rezurock has been well tolerated and adverse events have been consistent with those expected in patients with advanced cGVHD receiving corticosteroids and/or other immunosuppressants.

"We are proud to introduce Rezurock as a new treatment that uniquely addresses the underlying inflammatory and fibrotic pathophysiology of chronic GVHD," said Harlan W. Waksal, MD, President and CEO of Kadmon. "Thank you to the patients, their families and caregivers, who are the center of our focus in achieving this significant milestone. We have built a hematology/oncology-experienced commercial team and we look forward to rapid adoption of Rezurock for patients in need."

Rezurock is expected to be available in the United States by late August 2021.

Kadmon is committed to helping patients with treatment access and support. Kadmon ASSIST™ is a program designed to help and support Rezurock patients and their caregivers throughout their treatment journey. This program provides reimbursement assistance and savings programs for eligible patients. For more information, please call 1-844-KADMON1 (1-844-523-6661), Monday-Friday, 8:00 a.m.to 8:00 p.m. ET.

The NDA for Rezurock is part of Project Orbis, an initiative of the FDA Oncology Center of Excellence that provides a framework for concurrent submission and review of oncology drugs among participating international health authorities.

https://www.drugs.com/rezurock.html
https://en.wikipedia.org/wiki/Belumosudil

FDA Approves Rezurock (belumosudil) for the Treatment of Patients with Chronic Graft-Versus-Host Disease (cGVHD)

Saturday, July 24, 2021

Omega-3 Fatty Acids Tied to Better Cardiovascular Outcomes

In continuation of my update on Omega Fatty acids

Omega-3 fatty acids (FAs) are associated with lower cardiovascular mortality and improved cardiovascular outcomes, according to a review published online July 8 in eClinicalMedicine.

Safi U. Khan, M.B.B.S., from West Virginia University in Morgantown, and colleagues conducted a systematic literature review to determine the effectiveness of omega-3 FAs on fatal and nonfatal cardiovascular outcomes. The meta-analysis included 38 randomized controlled trials (149,051 participants) of omega-3 FAs, stratified by eicosapentaenoic acid (EPA) monotherapy and EPA + docosahexaenoic acid (DHA) therapy.

The researchers found that omega-3 FA intake was associated with reductions in cardiovascular mortality (rate ratio [RR], 0.93), nonfatal myocardial infarction (MI; RR, 0.87), coronary heart disease (CHD) events (RR, 0.91), major adverse cardiovascular events (MACE; RR, 0.95), and revascularization (RR, 0.91). EPA monotherapy was associated with higher risk reductions than EPA + DHA for cardiovascular mortality, nonfatal MI, CHD events, MACE, and revascularization. However, omega-3 FA increased incident atrial fibrillation (RR, 1.26), while EPA monotherapy was associated with a higher risk for total bleeding (RR, 1.49) and atrial fibrillation (RR, 1.35) compared with control.

"This study provides evidence regarding the therapeutic efficacy of omega-3 FAs and may explain the conflicting results between EPA monotherapy trials and those with EPA + DHA," the authors write.

Several authors disclosed financial ties to the pharmaceutical and biotechnology industries.



Omega-3 Fatty Acids Tied to Better Cardiovascular Outcomes 

Friday, July 23, 2021

Drug May Curb 'Sluggish' Thinking in Some Adults With ADHD

 

In continuation of my update on Lisdexamfetamine




Lisdexamfetamine reduces symptoms of sluggish cognitive tempo (SCT) in adults with attention-deficit/hyperactivity disorder (ADHD), according to a study published online June 29 in the Journal of Clinical Psychiatry.

In a randomized crossover trial, Lenard A. Adler, M.D., from NYU Langone Health in New York City, and colleagues assigned 38 adults with ADHD and SCT to either lisdexamfetamine or a placebo for four weeks.

The researchers found that lisdexamfetamine reduced symptoms of SCT by 30 percent. The drug also lowered ADHD symptoms by more than 40 percent. The drug improved both ADHD and SCT symptoms among the patients, compared to those who received the placebo. Furthermore, the investigators found that only about a quarter of overall improvements in SCT were due to improvements in ADHD symptoms.

"Adults with ADHD and comorbid SCT had significant improvement after lisdexamfetamine versus placebo in ratings of SCT, ADHD, executive function deficits, and functional impairment," the authors write. "This is the first study to show improvement in SCT after stimulant therapy in adults with ADHD."

The study was funded by Shire/Takeda Pharmaceuticals, the manufacturer of lisdexamfetamine.

https://en.wikipedia.org/wiki/Lisdexamfetamine

Thursday, July 22, 2021

Progress towards new treatments for tuberculosis

Boosting the body's own disease-fighting immune pathway could provide answers in the desperate search for new treatments for tuberculosis.



Tuberculosis still represents an enormous global disease burden and is one of the top 10 causes of death worldwide.

Led by WEHI's Dr. Michael Stutz and Professor Marc Pellegrini and published in Immunity, the study uncovered how cells infected with tuberculosis bacteria can die, and that using new medicines to enhance particular forms of cell death decreased the severity of the disease in a preclinical model.

Fighting antibiotic resistance

Tuberculosis is caused by bacteria that infect the lungs, spreading from person to person through the air. A challenge in the fight against tuberculosis is that the bacteria that cause the disease have developed resistance to most antibiotic treatments, leading to a need for new treatment approaches.

Tuberculosis bacteria grow within immune cells in the lungs. One of the ways that cells protect against these 'intracellular' pathogens is to undergo a form of cell death called apoptosis—destroying the cell as well as the microbes within it.

Using preclinical models, researchers sequentially deleted key apoptosis effectors, to demonstrate their roles in controlling tuberculosis infections. This demonstrated that a proportion of tuberculosis-infected cells could die by apoptosis—opening up new opportunities for controlling the disease.

Using host-directed therapies to reduce disease burden

Dr. Stutz said researchers then tested new drugs that force cells to die. This revealed that a drug-like compound that inhibits cell death-regulatory proteins called IAPs could promote death of the infected cells.

"When we treated our infection models with this compound, we were able to significantly reduce the amount of tuberculosis disease," he said.

"The longer the treatment was used, the greater the reduction of disease."

The research team was able to replicate these results using various different IAP inhibitors.

"Excitingly, many of these compounds are already in clinical trials for other types of diseases and have proven to be safe and well-tolerated by patients," Dr. Stutz said.

"We predict that if these compounds were progressed for treating tuberculosis, they would be most effective if used alongside existing antibiotic treatments."

Opening the door to new treatment methods

Professor Marc Pellegrini said until now,  were the only treatment for tuberculosis, which were limited in their application due to increasing antibiotic resistance.

"Unlike antibiotics, which directly kill , IAP inhibitors kill the  that the  need to survive," he said.

"The beauty of using a host-directed therapy is that it doesn't directly target the microbe, it targets a host process. By targeting the host rather than the microbe, the chances of resistance developing are incredibly low."

The team hope the research will lead to better treatments for tuberculosis.

"This research increases our understanding of the types of immune responses that are beneficial to us, and this is an important step towards new treatments for tuberculosis, very few of which have been developed in the last 40 years," Dr. Stutz said.

"We have demonstrated that host-directed therapies are viable for infections such as , which is particularly important in the era of extensive antibiotic resistance."

https://www.sciencedirect.com/science/article/abs/pii/S1074761321002533?via%3Dihub

Wednesday, July 21, 2021

Oral Transglutaminase 2 Inhibitor Beneficial in Celiac Disease

For patients with celiac disease, treatment with a selective oral transglutaminase 2 inhibitor (ZED1227) attenuates gluten-induced duodenal mucosal damage, according to a study published in the July 1 issue of the New England Journal of Medicine.


Detlef Schuppan, M.D., Ph.D., from the Johannes Gutenberg University in Mainz, Germany, and colleagues conducted a proof-of-concept trial of a six-week treatment with ZED1227 at three dose levels versus placebo among adults with well-controlled celiac disease who underwent a daily gluten challenge. The primary end point of attenuation of gluten-induced mucosal damage was assessed among 35, 39, 38, and 30 patients assigned to 10-mg, 50-mg, and 100-mg ZED1227 and placebo, respectively.

The researchers found that at all three dose levels, ZED1227 treatment attenuated gluten-induced duodenal mucosal injury. From baseline to week six, the mean ratio of villus height to crypt depth estimated difference from placebo was 0.44, 0.49, and 0.48 in the 10-, 50-, and 100-mg groups, respectively. For the change in intraepithelial lymphocyte density, the estimated differences from placebo were −2.7, −4.2, and −9.6 cells per 100 epithelial cells, respectively, for 10-, 50-, and 100-mg ZED1227. Symptom and quality-of-life scores may have been improved with use of the 100-mg dose.

"Although this trial is very encouraging, whether treatment with ZED1227, and more generally transglutaminase 2 inhibition, in patients with celiac disease will be efficient in real life and during long-term gluten exposure remains to be determined," writes the author of an accompanying editorial.

https://www.medchemexpress.com/zed-1227.html